Effects of the Cyclooxygenase Inhibitor Ibuprofen on Retinal and Choroidal Blood Flow during Hyperoxia in Newborn Piglets

Abstract

Purpose: The effect of the cyclooxygenase inhibitor ibuprofen (IB) on choroidal (ChBF) and retinal (RBF) blood flow during hyperoxia was examined in 21 spontaneously breathing newborn piglets. Methods: ChBF and RBF were measured using radiolabelled microspheres before and 30 min after either saline or IB (30 mg/kg, IV) infusion in room air and subsequently, after 90 min of hyperoxia (O₂). Results: The basal RBF and ChBF did not change after IB infusion. However, during hyperoxia a significant decrease in RBF was observed in the IB group (54 ± 5 to 37 ± 3 ml/min/100gp < 0.02) and in the control group (54 ± 3 to 37 ± 5 ml/min/100g, p < 0.02). Also, ChBF decreased in the IB group (2,635 ± 446 to 1,670 ± 199 ml/min/100 g, p < 0.02) and in the control group, (2,997 ± 346 to 2,014 ± 246 ml/min/100 g, p < 0.02) during hyperoxia. Conclusions: Despite cyclooxygenase inhibition with IB, RBF and ChBF decreased to the same extent as in the control group following exposure to O₂ These data suggest that hyperoxia decrease RBF and ChBF through mechanisms and/or mediators other than the cyclooxygenase by-products of arachidonic acid metabolism.

Mechanisms of Hyperoxia-Induced Reductions in Retinal Blood Flow in Newborn Pig

“…The present results indicating a substantial involvement of thromboxane differ from the conclusion advanced in a recent study by Stiris et al (1996), wherein the cyclooxygenase inhibitor ibuprofen did not affect the status of RBF in the piglet after 90 min of sustained hyperoxia. Although piglets were studied in each instance, the respective drugs chosen for thromboxane inhibition represent important differences between these studies.…”

“…In our model, calculated RBF decreased 42 % during the initial 20 min of 100 % oxygen breathing. The magnitude of this response was similar to that measured in piglets with microspheres by Hardy et al (1996) (44 %) and Stiris et al (1996) (32 %) after 45 and 90 min of sustained hyperoxia, respectively. The mechanistic basis for this retinal response to elevated PaO # has yet to be systematically clarified.…”

“…enzyme system, are potent vasoconstrictors. A role for thromboxane in the ocular hemodynamics of the chronically hyperoxic neonate was long ago hypothesized (Flower et al, 1984), but a recent finding that cyclooxygenase inhibition by ibuprofen was without effect on acute reductions in retinal blood flow in newborn piglets (Stiris et al, 1996) led to the reexamination of this issue with a specific thromboxane synthesis inhibitor and receptor antagonist. Recent studies in brain and other organs have documented vasoconstriction by exogenous 20-HETE, an arachidonic acid metabolite of the P %&!…”

Effect of the cyclo‐oxygenase blocker ibuprofen on cerebral blood volume and cerebral blood flow during normocarbia and hypercarbia in newborn piglets

“…This difference apparently depended on whether or not the animals were paralysed with pancuronium. Inasmuch as ibuprofen did not alter cardiac output in previous studies (22), we think that the increase in cardiac output observed in the ibuprofen-treated animals in this study is a confounder and did not influence the results. We do not think that increased cardiac output explains the increase in CBF and DCBV in response to CO 2 changes because the slight increase in cardiac output probably produced the slight increase in arterial blood pressure observed in the ibuprofen-treated animals.…”

“…We did not measure cerebral prostanoids in this experiment, but data previously obtained in our laboratory (22) have shown a significant and sustained reduction of prostanoid synthesis in vitreous 120 min after ibuprofen administration.…”